The overall goal of the City of Hope Lymphoma SPORE is to develop translational studies to improve the treatment of Hodgkin and non-Hodgkin lymphoma. This application, consisting of four translational research projects and four cores, will develop novel approaches that are derived from molecular and immunologic studies in lymphoma and T-cell and antibody-based therapies. An important theme of the translational studies in this grant is to develop effective therapeutics for lymphoma that will reduce toxicities associated with current treatment regimens for Hodgkin and non-Hodgkin Lymphoma which can be utilized for treatment of older patients. Project 1 will study the effectiveness of cellular immunotherapy for B cell lymphoma utilizing engineered central memory derived CD19-specific T-cells. Investigators in this project have developed a T-cell genetic modification platform for expressing chimeric immunoreceptors that redirect antigen specificity and effector function of central memory T-cells towards cell surface epitopes on B cell lymphomas and will test the persistence and expansion of these cells after infusion. Because epidemiologic Studies indicate that stem cell damage from pretransplant therapeutic exposures may play a role in the subsequent development of myelodysplasia, Project 2 will longitudinally study a population of patients with Hodgkin and non-Hodgkin Lymphoma. The investigators will continue their studies of the cellular and molecular factors that are predictive for development of myelodysplasia, and to determine the molecular sequence of events that lead to this complication of treatment. In Project 3 investigators will test a molecularly engineered novel anti-CD20 IL-2 immunocytokine for the treatment of patients with 0020^ lymphoma. An important component of this project will be to delineate the immunologic effector mechanisms operative in immunocytokine-mediated anti-lymphoma in vivo activity. Project 4 will develop siRNA based therapeutics against transcription factors (STATS) important in lymphoma behavior using an antibody directed cyclodextrin nanoparticle for treatment of patients with B cell lymphoma. The projects in this Lymphoma SPORE will be supported by four cores including: Administration, Biostatistics and Research Informatics, Tissue Bank for Molecular and Cellular Studies, and Biological Manufacturing. This Lymphoma SPORE will also support a Developmental Research Program and a Career Development Program to foster the advancement of pilot translational research projects and young investigators focused on lymphoma.